tbuckley/cabot-search huggingface dataset:
Esophageal endoscopic submucosal dissection using a novel thin therapeutic scope for early esophageal cancer adjacent to chemoradiotherapy-induced stricture
Authors: Kurato Miyazaki, Motohiko Kato, Takanori Kanai, Naohisa Yahagi
Journal: Endoscopy (2023)

Metachronous esophageal cancers frequently occur, but endoscopic submucosal dissection (ESD) for lesions that occur adjacent to post-treatment scars are often challenging. Furthermore, in cases involving post-treatment stricture, endoscopic balloon dilation or scar incision may be required before ESD, so synchronous ESD for such lesions are even more challenging. Recently, a novel therapeutic thin endoscope, the EG-840TP (Fujifilm, Tokyo, Japan), has been developed. This scope has a thinner outer diameter (7.9 mm) and more adequate down angle (160°) than a conventional therapeutic scope ([Fig. 1, ] [Fig. 2]). We report a very successful case of ESD using this scope for a superficial esophageal cancer adjacent to a chemoradiotherapy-induced stricture ([Video 1]).
An overview of in vitro 3D models of the blood-brain barrier as a tool to predict the in vivo permeability of nanomedicines
Authors: Alexandre Pérez-López, Ana Isabel Torres-Suárez, Cristina Martín-Sabroso, Juan Aparicio-Blanco
Journal: Advanced Drug Delivery Reviews (2023)

The blood-brain barrier (BBB) prevents efficient drug delivery to the central nervous system. As a result, brain diseases remain one of the greatest unmet medical needs. Understanding the tridimensional structure of the BBB helps gain insight into the pathology of the BBB and contributes to the development of novel therapies for brain diseases. Therefore, 3D models with an ever-growing sophisticated complexity are being developed to closely mimic the human neurovascular unit. Among these 3D models, hydrogel-, spheroid- and organoid-based static BBB models have been developed, and so have microfluidic-based BBB-on-a-chip models. The different 3D preclinical models of the BBB, both in health and disease, are here reviewed, from their development to their application for permeability testing of nanomedicines across the BBB, discussing the advantages and disadvantages of each model. The validation with data from in vivo preclinical data is also discussed in those cases where provided.
Systemic immune dysregulation in severe tuberculosis patients revealed by a single-cell transcriptome atlas
Authors: Yi Wang, Qing Sun, Yun Zhang, Xuelian Li, Qingtao Liang, Ru Guo, Liqun Zhang, Xiqin Han, Jing Wang, Lingling Shao, Yu Xue, Yang Yang, Hua Li, Lihui Nie, Wenhui Shi, Qiuyue Liu, Jing Zhang, Hongfei Duan, Hairong Huang, Laurence Don Wai Luu, Jun Tai, Xinting Yang, Guirong Wang
Journal: Journal of Infection (2023)

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb) infection, is currently the deadliest infectious disease in human that can evolve to severe forms. A comprehensive immune landscape for Mtb infection is critical for achieving TB cure, especially for severe TB patients. We performed single-cell RNA transcriptome and T-cell/B-cell receptor (TCR/BCR) sequencing of 213,358 cells from 27 samples, including 6 healthy donors and 21 active TB patients with varying severity (6 mild, 6 moderate and 9 severe cases). Two published profiles of latent TB infection were integrated for the analysis. We observed an obviously elevated proportion of inflammatory immune cells (e.g., monocytes), as well as a markedly decreased abundance of various lymphocytes (e.g., NK and γδT cells) in severe patients, revealing that lymphopenia might be a prominent feature of severe disease. Further analyses indicated that significant activation of cell apoptosis pathways, including perforin/granzyme-, TNF-, FAS- and XAF1-induced apoptosis, as well as cell migration pathways might confer this reduction. The immune landscape in severe patients was characterized by widespread immune exhaustion in Th1, CD8+T and NK cells as well as high cytotoxic state in CD8+T and NK cells. We also discovered that myeloid cells in severe TB patients may involve in the immune paralysis. Systemic upregulation of S100A12 and TNFSF13B, mainly by monocytes in the peripheral blood, may contribute to the inflammatory cytokine storms in severe patients. Our data offered a rich resource for understanding of TB immunopathogenesis and designing effective therapeutic strategies for TB, especially for severe patients.
Nasopharyngeal swabs as alternative specimens for the diagnosis of dengue virus infection
Authors: Alícia Cavalcante Maia, Tatyane de Souza Cardoso Quintão, Pâmela Maria de Oliveira, Évelin Mota Cassemiro, Daiani Cristina Cilião-Alves, Priscilla Pedrette de Melo Alves, Fabiano dos Anjos Pereira Martins, Emerson Luiz Lima Araújo, Helen da Costa Gurgel, Elza Ferreira Noronha, Walter Massa Ramalho, Alex Leite Pereira, Svetoslav Nanev Slavov, Wildo Navegantes de Araújo, Rodrigo Haddad
Journal: Journal of Infection (2023)
Antiviral effect of azvudine and nirmatrelvir-ritonavir among hospitalized patients with COVID-19
Authors: Yuan Gao, Zujin Luo, Shan Ren, Zhonghui Duan, Ying Han, Huihang Liu, Ziwen Gao, Xinyu Zhang, Zhongjie Hu, Yingmin Ma
Journal: Journal of Infection (2023)
Quality of life of Bangladeshi children and young adults with atopic eczema and their families in East London
Journal: British Journal of Dermatology (2023)

Journal Article Quality of life of Bangladeshi children and young adults with atopic eczema and their families in East London Get access British Journal of Dermatology, Volume 188, Issue 4, April 2023, Page e33, https://doi.org/10.1093/bjd/ljad051 Published: 30 March 2023
Parent and child experiences of skin conditions and views on mindfulness-based support
Journal: British Journal of Dermatology (2023)

Journal Article Parent and child experiences of skin conditions and views on mindfulness-based support Get access British Journal of Dermatology, Volume 188, Issue 4, April 2023, Page e32, https://doi.org/10.1093/bjd/ljad052 Published: 30 March 2023
Communication of anticancer drug benefits and related uncertainties to patients and clinicians: document analysis of regulated information on prescription drugs in Europe
Authors: Courtney Davis, Anita K Wagner, Maximilian Salcher-Konrad, Henry Scowcroft, Barbara Mintzes, Adrian M J Pokorny, Jianhui Lew, Huseyin Naci
Journal: BMJ (2023)

Abstract Objective To evaluate the frequency with which relevant and accurate information about the benefits and related uncertainties of anticancer drugs are communicated to patients and clinicians in regulated information sources in Europe. Design Document content analysis. Setting European Medicines Agency. Participants Anticancer drugs granted a first marketing authorisation by the European Medicines Agency, 2017-19. Main outcome measures Whether written information on a product addressed patients’ commonly asked questions about: who and what the drug is used for; how the drug was studied; types of drug benefit expected; and the extent of weak, uncertain, or missing evidence for drug benefits. Information on drug benefits in written sources for clinicians (summaries of product characteristics), patients (patient information leaflets), and the public (public summaries) was compared with information reported in regulatory assessment documents (European public assessment reports). Results 29 anticancer drugs that received a first marketing authorisation for 32 separate cancer indications in 2017-19 were included. General information about the drug (including information on approved indications and how the drug works) was frequently reported across regulated information sources aimed at both clinicians and patients. Nearly all summaries of product characteristics communicated full information to clinicians about the number and design of the main studies, the control arm (if any), study sample size, and primary measures of drug benefit. None of the patient information leaflets communicated information to patients about how drugs were studied. 31 (97%) summaries of product characteristics and 25 (78%) public summaries contained information about drug benefits that was accurate and consistent with information in regulatory assessment documents. The presence or absence of evidence that a drug extended survival was reported in 23 (72%) summaries of product characteristics and four (13%) public summaries. None of the patient information leaflets communicated information about the drug benefits that patients might expect based on study findings. Scientific concerns about the reliability of evidence on drug benefits, which were raised by European regulatory assessors for almost all drugs in the study sample, were rarely communicated to clinicians, patients, or the public. Conclusions The findings of this study highlight the need to improve the communication of the benefits and related uncertainties of anticancer drugs in regulated information sources in Europe to support evidence informed decision making by patients and their clinicians.
Temperate bacteriophages infecting the mucin-degrading bacterium <i>Ruminococcus gnavus</i> from the human gut
Authors: Colin Buttimer, Ekaterina V. Khokhlova, Lisa Stein, Cara M. Hueston, Bianca Govi, Lorraine A. Draper, R. Paul Ross, Andrey N. Shkoporov, Colin Hill
Journal: Gut Microbes (2023)

Ruminococcus gnavus is a prevalent gut microbe reported to occur in higher abundance among individuals with inflammatory bowel disease (IBD). This study reports the isolation and characterization of six bacteriophages (phages) isolated from human fecal material and environmental samples that infect this species. Isolated phages have a siphovirus morphology, with genomes ranging between 36.5 and 37.8 kbp. Genome analysis indicates that the phages have a temperate lifestyle, which was confirmed by their ability to form lysogens on their host bacterial species. In contrast to the finding that phages lyse their host in liquid medium, results from a mouse trial indicate these phages can co-exist with the host bacterium in the gut without causing a significant reduction of R. gnavus. The bacterial counts in the feces of phage-treated mice did not significantly differ in the presence of phage. Furthermore, analysis of publicly available gut virome sequence data indicates a high abundance of these phages among individuals suffering from IBD. This work provides the first insight into how phages interact with R. gnavus in the human gut microbiome.
“Using chest computed tomography and unsupervised machine learning for predicting and evaluating response to lumacaftor–ivacaftor in people with cystic fibrosis.” A. Campredon, E. Battistella, C. Martin,<i>et al.</i><i>Eur Respir J</i>2022; 59: 2101344.
Journal: European Respiratory Journal (2023)

Due to mistakes in tabulating data when preparing the manuscript, the original published version of this article contained errors in the description of the clustering cohort in tables 1 and 3.After reviewing all the data and analysis, the authors concluded that the analysis was performed correctly and that these errors do not change the main message of the published study.In the same section, in the following the sentence the p-value has changed from p=0.01 to p=0.02: "Interestingly, patients from cluster C, who had less morphologically and functionally severe disease, were better responders to treatment than the others (54% of responders in cluster C versus 32% in cluster A and 33% in cluster B, p=0.02).
Cemiplimab Plus Chemotherapy Versus Chemotherapy Alone in Advanced NSCLC: 2-Year Follow-Up From the Phase 3 EMPOWER-Lung 3 Part 2 Trial
Authors: Tamta Makharadze, Miranda Gogishvili, Tamar Melkadze, Ana Baramidze, Davit Giorgadze, Konstantin Penkov, Konstantin Laktionov, Gia Nemsadze, Marina Nechaeva, Irina Rozhkova, Ewa Kalinka, Siyu Li, Yuntong Li, Manika Kaul, Ruben G.W. Quek, Jean-Francois Pouliot, Frank Seebach, Israel Lowy, Giuseppe Gullo, Petra Rietschel
Journal: Journal of Thoracic Oncology (2023)

EMPOWER-Lung 3 part 2 (NCT03409614), a double-blind, placebo-controlled phase 3 study, investigated cemiplimab (antiprogrammed cell death protein 1) plus chemotherapy versus placebo plus chemotherapy in patients with advanced NSCLC without EGFR, ALK, or ROS1 aberrations, with either squamous or nonsquamous histology, irrespective of programmed death-ligand 1 levels. At primary analysis, after 16.4 months of follow-up, cemiplimab plus chemotherapy improved median overall survival (OS) versus chemotherapy alone (21.9 versus 13.0 mo, hazard ratio [HR] = 0.71, 95% confidence interval [CI]: 0.53-0.93, p = 0.014). Here, we report protocol-specified final OS and 2-year follow-up results. Patients (N = 466) were randomized 2:1 to receive histology-specific platinum-doublet chemotherapy, with 350 mg cemiplimab (n = 312) or placebo (n = 154) every 3 weeks for up to 108 weeks. Primary end point was OS; secondary end points included progression-free survival and objective response rates. After 28.4 months of median follow-up, median OS was 21.1 months (95% CI: 15.9-23.5) for cemiplimab plus chemotherapy versus 12.9 months (95% CI: 10.6-15.7) for chemotherapy alone (HR = 0.65, 95% CI: 0.51-0.82, p = 0.0003); median progression-free survival was 8.2 months (95% CI: 6.4-9.0) versus 5.5 months (95% CI: 4.3-6.2) (HR = 0.55, 95% CI: 0.44-0.68, p < 0.0001), and objective response rates were 43.6% versus 22.1%, respectively. Safety was generally consistent with previously reported data. Incidence of treatment-emergent adverse events of grade 3 or higher was 48.7% with cemiplimab plus chemotherapy and 32.7% with chemotherapy alone. At protocol-specified final OS analysis with 28.4 months of follow-up, the EMPOWER-Lung 3 study continued to reveal benefit of cemiplimab plus chemotherapy versus chemotherapy alone in patients with advanced squamous or nonsquamous NSCLC, across programmed death-ligand 1 levels.
Hiding in plain sight: the evolving definition of chronic breathlessness and new ICD-11 wording
Authors: Slavica Kochovska, Magnus Ekström, John Hansen-Flaschen, Diana Ferreira, Thomas Similowski, Miriam J. Johnson, David C. Currow
Journal: European Respiratory Journal (2023)

<b>The International Classification of Disease (ICD-11) has adopted three timeframes for dyspnoea: acute, subacute and chronic, the latter despite underlying causes being optimally treated. Breathlessness, a word patients use, is now a synonym for dyspnoea.</b> https://bit.ly/3Z2qNya
Journal Club
Journal: Arthritis & Rheumatology (2023)

Daily Prednisone and TCZ Treatment of GCA Affects HbA 1cClinicians have established hemoglobin A 1c (HbA 1c ) as a convenient marker for the diagnosis and monitoring of diabetes.While researchers lack a thorough understanding of the relationship between red blood cell (RBC) count and inflammation, some tory factors may lead to an increased number of young RBCs, which may, in turn, reduce HbA 1c in a glucose-independent manner.Consistent with this hypothesis is the fact that previous studies have documented a quick rise in HbA 1c levels when initiating glucocorticoids (GCs).In this issue, Patel et al (p.586) report that tocilizumab (TCZ) treatment of giant cell arteritis was associated with a substantial reduction in HbA 1c level.The investigators sought to understand the impact of a GC taper and TCZ treatment on HbA 1c levels and analyzed the systematic data collected during the clinical trial of TCZ in GCA known as GiACTA.The detailed longitudinal data spanned 52 weeks and revealed that HbA 1c decreased as the GC daily dose
Clinical Connections
Journal: Arthritis & Rheumatology (2023)

No measures are presently available for early diagnosis of osteoarthritis (OA), before destructive changes are observable on radiographs, and there are no disease-modifying drugs marketed for OA.A biomarker that is associated with disease occurrence and/or progression would help to identify cases earlier and monitor the disease course.This could greatly support development of effective therapies for this disease.
Lineage tracing reveals clonal progenitors and long-term persistence of tumor-specific T cells during immune checkpoint blockade
Authors: Joy A. Pai, Matthew D. Hellmann, Jennifer L. Sauter, Marissa Mattar, Hira Rizvi, Hyung Jun Woo, Nisargbhai Shah, Evelyn M. Nguyen, Fathema Z. Uddin, Alvaro Quintanal-Villalonga, Joseph M. Chan, Parvathy Manoj, Viola Allaj, Marina K. Baine, Umesh K. Bhanot, Mala Jain, Irina Linkov, Fanli Meng, David Brown, Jamie E. Chaft, Andrew J. Plodkowski, Mathieu Gigoux, Helen H. Won, Triparna Sen, Daniel K. Wells, Mark T.A. Donoghue, Elisa de Stanchina, Jedd D. Wolchok, Brian Loomis, Taha Merghoub, Charles M. Rudin, Andrew Chow, Ansuman T. Satpathy
Journal: Cancer Cell (2023)
The orphan receptor Nur77 binds cytoplasmic LPS to activate the non-canonical NLRP3 inflammasome
Authors: Fangrui Zhu, Juan Ma, Weitao Li, Qiannv Liu, Xiwen Qin, Yan Qian, Chunlei Wang, Yan Zhang, Yi Li, Dong Jiang, Shuo Wang, Pengyan Xia
Journal: Immunity (2023)
Modulating fast skeletal muscle contraction protects skeletal muscle in animal models of Duchenne muscular dystrophy
Authors: Alan J. Russell, Mike DuVall, Ben Barthel, Ying Qian, Angela K. Peter, Breanne L. Newell-Stamper, Kevin Hunt, Sarah Lehman, Molly Madden, Stephen Schlachter, Ben Robertson, Ashleigh Van Deusen, Hector M. Rodriguez, Carlos Vera, Yu Su, Dennis R. Claflin, Susan V. Brooks, Peter Nghiem, Alexis Rutledge, Twlya I. Juehne, Jinsheng Yu, Elisabeth R. Barton, Yangyi E. Luo, Andreas Patsalos, Laszlo Nagy, H. Lee Sweeney, Leslie A. Leinwand, Kevin Koch
Journal: Journal of Clinical Investigation (2023)

Duchenne muscular dystrophy (DMD) is a lethal muscle disease caused by absence of the protein dystrophin, which acts as a structural link between the basal lamina and contractile machinery to stabilize muscle membranes in response to mechanical stress. In DMD, mechanical stress leads to exaggerated membrane injury and fiber breakdown, with fast fibers being the most susceptible to damage. A major contributor to this injury is muscle contraction, controlled by the motor protein myosin. However, how muscle contraction and fast muscle fiber damage contribute to the pathophysiology of DMD has not been well characterized. We explored the role of fast skeletal muscle contraction in DMD with a potentially novel, selective, orally active inhibitor of fast skeletal muscle myosin, EDG-5506. Surprisingly, even modest decreases of contraction (<15%) were sufficient to protect skeletal muscles in dystrophic mdx mice from stress injury. Longer-term treatment also decreased muscle fibrosis in key disease-implicated tissues. Importantly, therapeutic levels of myosin inhibition with EDG-5506 did not detrimentally affect strength or coordination. Finally, in dystrophic dogs, EDG-5506 reversibly reduced circulating muscle injury biomarkers and increased habitual activity. This unexpected biology may represent an important alternative treatment strategy for Duchenne and related myopathies.
Complement C3a treatment accelerates recovery after stroke via modulation of astrocyte reactivity and cortical connectivity
Authors: Anna Stokowska, Markus Aswendt, Daniel Zucha, Stephanie Lohmann, Frederique Wieters, Javier Morán Suarez, Alison L. Atkins, YiXian Li, Maria Miteva, Julia Lewin, Dirk Wiedermann, Michael Diedenhofen, Åsa Torinsson Naluai, Pavel Abaffy, Lukas Valihrach, Mikael Kubista, Mathias Hoehn, Milos Pekny, Marcela Pekna
Journal: Journal of Clinical Investigation (2023)

Despite advances in acute care, ischemic stroke remains a major cause of long-term disability. Approaches targeting both neuronal and glial responses are needed to enhance recovery and improve long-term outcome. The complement C3a receptor (C3aR) is a regulator of inflammation with roles in neurodevelopment, neural plasticity, and neurodegeneration. Using mice lacking C3aR (C3aR-/-) and mice overexpressing C3a in the brain, we uncovered 2 opposing effects of C3aR signaling on functional recovery after ischemic stroke: inhibition in the acute phase and facilitation in the later phase. Peri-infarct astrocyte reactivity was increased and density of microglia reduced in C3aR-/- mice; C3a overexpression led to the opposite effects. Pharmacological treatment of wild-type mice with intranasal C3a starting 7 days after stroke accelerated recovery of motor function and attenuated astrocyte reactivity without enhancing microgliosis. C3a treatment stimulated global white matter reorganization, increased peri-infarct structural connectivity, and upregulated Igf1 and Thbs4 in the peri-infarct cortex. Thus, C3a treatment from day 7 after stroke exerts positive effects on astrocytes and neuronal connectivity while avoiding the deleterious consequences of C3aR signaling during the acute phase. Intranasal administration of C3aR agonists within a convenient time window holds translational promise to improve outcome after ischemic stroke.
Not Only Excruciating Pain: Might a Gout Flare Episode Lead to Pulmonary Embolism?
Authors: Hyon K. Choi, Yuqing Zhang
Journal: Arthritis & Rheumatology (2023)

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Laparoscopic vs Open Surgery for Low Rectal Cancer—Reply
Authors: Wei-Zhong Jiang, Yan-Wu Sun, Pan Chi
Journal: JAMA Oncology (2023)

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